Cerebrovascular disease is one of the leading causes of death in the USA, with more than 140,000 people dying each year from a stroke. While age remains the greatest risk factor for stroke, other conditions are also known to predispose individuals, including hypertension, obesity, and diabetes. Other comorbid conditions, such as coagulopathies, congenital heart disease and sickle cell disease (SCD), render both adults and children vulnerable to ischemic stroke. For example, about 24% of SCD patients have a stroke by the age of 45 and 11% by the age of 20. Based on our preliminary findings and evidence already in the literature, this project will use pharmacological and genetic approaches to address the important role that neutrophils play in blood flow impairment in the cerebral microvasculature that is associated with SCD. Overall the results obtained will lead to further understanding the prothrombogenic phenotype of SCD and the potential implication of targeting neutrophils as a therapeutic strategy and treatment for this debilitating and life threatening disease.